The overall objective of the Computational Genomics Core is to use the state-of-the-art mathematical and computational approaches needed to better understand the complex systems biology presented by injury and critical illness. In addition, built on our developments and experiences in computational biology in the Inflammation and the Host Response to Injury Glue Grant, the Core is also designed to tackle several current computational challenges in translational research of injury. The major functions of the core are: (1) Investigate via computational analyses the genomic mechanism of the adaptive and maladaptive physiological responses to thermo injury in studies of the Research Projects, (la) Develop computational tools for using new exon-junction arrays in detection of gene expression and alternative splicing in animal models (mouse and Rhesus monkeys);(1b) Analyze the genomic effect of activation and/or inhibition of genes important to insulin resistance and mitochondrial dysfunction in animal models;and (1c) Compare cross species the genomic changes between animal models and burn patients, and between LPS and burns. Our goal in this program is using computational analysis to comprehensively identify and catalog the similarities and differences between these inflammatory sources and between patients and model systems. (2) Integrate the genomic, protein activity and metabolic data of the Center for rational target identification of gene candidates for intervention. (2a) Establish a disease specific knowledge-base of molecular derangements in skeletal muscle following thermal injury by integrating findings of the Center Projects with the information systematically harvested from the literature as well as the human transcriptome data of burn patients;(2b) Conduct computational analysis to identify key gene regulators as candidates for intervention studies. (3) Establish web-based portal of the data and knowledgebase as central community resource. Data warehousing and providing web-accessible sharing of the data and results with the research community. Importantly, the successful accomplishments will be achieved by the multidisciplinary group effort of close collaborations between bioinformaticians and statisticians, and the other investigators in the Center.

Public Health Relevance

The Computational Genomics Core will develop and apply mathematical and computational methods to analyze, integrate, and share the large amount of research data and findings from the Center as well as the research community in order to understand the molecular mechanism of burn injury and subsequently help identify new targets for intervention. The ultimate goal is to search for better treatments of thermo injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM021700-33
Application #
8668974
Study Section
Special Emphasis Panel (ZGM1-PPBC-5)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
33
Fiscal Year
2014
Total Cost
$193,793
Indirect Cost
$81,235
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Tao, Rongya; Wang, Caixia; Stöhr, Oliver et al. (2018) Inactivating hepatic follistatin alleviates hyperglycemia. Nat Med 24:1058-1069
Nakazawa, Harumasa; Chang, Kyungho; Shinozaki, Shohei et al. (2017) iNOS as a Driver of Inflammation and Apoptosis in Mouse Skeletal Muscle after Burn Injury: Possible Involvement of Sirt1 S-Nitrosylation-Mediated Acetylation of p65 NF-?B and p53. PLoS One 12:e0170391
Frydman, Galit H; Marini, Robert P; Bakthavatchalu, Vasudevan et al. (2017) Local and Systemic Changes Associated with Long-term, Percutaneous, Static Implantation of Titanium Alloys in Rhesus Macaques (Macaca mulatta). Comp Med 67:165-175
Khan, Mohammed A S; Khan, Mohammed F; Kashiwagi, Shizuka et al. (2017) An ALPHA7 Nicotinic Acetylcholine Receptor Agonist (GTS-21) Promotes C2C12 Myonuclear Accretion in Association with Release of Interleukin-6 (IL-6) and Improves Survival in Burned Mice. Shock 48:227-235
Li, Peng; Tompkins, Ronald G; Xiao, Wenzhong et al. (2017) KERIS: kaleidoscope of gene responses to inflammation between species. Nucleic Acids Res 45:D908-D914
Kashiwagi, Shizuka; Khan, Mohammed A S; Yasuhara, Shingo et al. (2017) Prevention of Burn-Induced Inflammatory Responses and Muscle Wasting by GTS-21, a Specific Agonist for ?7 Nicotinic Acetylcholine Receptors. Shock 47:61-69
Ueki, Ryusuke; Liu, Li; Kashiwagi, Shizuka et al. (2016) Role of Elevated Fibrinogen in Burn-Induced Mitochondrial Dysfunction: Protective Effects of Glycyrrhizin. Shock 46:382-9
Agarwal, Shailesh; Loder, Shawn; Brownley, Cameron et al. (2016) Inhibition of Hif1? prevents both trauma-induced and genetic heterotopic ossification. Proc Natl Acad Sci U S A 113:E338-47
Shank, Erik S; Martyn, Jeevendra A; Donelan, Mathias B et al. (2016) Ultrasound-Guided Regional Anesthesia for Pediatric Burn Reconstructive Surgery: A Prospective Study. J Burn Care Res 37:e213-7
Copps, Kyle D; Hançer, Nancy J; Qiu, Wei et al. (2016) Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase. J Biol Chem 291:8602-17

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